RESUMEN
BACKGROUND: We previously cloned prosaposin (PSAP) from metastatic castrate-resistant prostate cancer (mCRPCa) cells and demonstrated its genomic amplification and/or overexpression in metastatic PCa cell lines, xenografts, and lymph node metastases. The clinicohistopathological significance of serum PSAP levels and its tissue expression and association with predictive or prognostic variable in primary or advanced PCa are not known. METHODS: We examined PSAP expression by immunohistochemical staining during early embryogenic development of the prostate and within a large tissue microarray which included 266 benign and malignant prostate tissues. In addition, serum PSAP levels in the age-adjusted normal male population and in 154 normal individuals and patients with primary or mCRPCa were measured by an ELISA assay. RESULTS: Univariate and multivariate analyses revealed a significant and inverse association between PSAP expression and clinical stages II and III tumors, dominant Gleason patterns 3 and 4, and seminal vesicle invasion. In the normal male population, the lowest serum PSAP level was detected before puberty, peaked at the most reproductive age group (20- to 39-year old), and then, decreased to a range between the two groups for men above 40-year old. Regardless of age and when compared with normal individuals, serum PSAP levels significantly decreased in primary organ-confined PCa, but increased in those with mCRPCa. CONCLUSION: Our results show that PSAP has the potential to differentiate between primary and advanced PCa. Additional large-scale studies are needed to define the usefulness of tissue expression or serum PSAP levels as a diagnostic or prognostic marker or as a therapeutic target in PCa.